Allosteric Kinase Inhibitors Library contains 26,000 compounds that target allosteric pockets of kinases. Allosteric inhibition offers a promising alternative to targeting the highly conserved ATP-binding pocket of kinases, which can pose challenges in terms of selectivity and drug resistance.
While the number of identified allosteric inhibitors is smaller compared to inhibitors targeting the ATP pocket, there have been encouraging advancements in this area. For example, the FDA-approved small-molecule allosteric inhibitor trametinib in 2013 demonstrated the potential of allosteric inhibition. Additionally, more than 10 other allosteric inhibitors are currently in clinical trials, and there is a pipeline of highly selective and potent preclinical molecules.
This library provides researchers with a valuable collection of compounds that can target allosteric pockets of kinases, offering potential solutions to overcome the limitations of ATP pocket-targeting inhibitors. By targeting these allosteric sites, researchers can potentially achieve improved selectivity and overcome issues related to drug resistance.
[1] C. Zhuang, R. V. Vishnudas, and J. Fang, “Targeting Protein Kinase Allosteric Pocket: A Promising Alternative for Kinase Inhibition,” Acta Pharmaceutica Sinica B, vol. 9, no. 5, pp. 942-952, Sep. 2019, doi: 10.1016/j.apsb.2019.01.012.
